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The use of chewing tobacco is a severe risk factor for oral mucosa related diseases including cancer in India as well as USA, although its relationship with Oral Leukoplakia (OL) or related carcinogenicity is still not clear. This work chose two oncogenic pathway proteins- the Epidermal Growth Factor Receptor and the WNT pathway among leukoplakia patients and established their correlation with the individuals' tobacco chewing habit. 89 fresh patients with OL were selected for the work. The samples were classified based on the individual's tobacco chewing habit. The divided samples were then immunostained with antibodies for both of the EGFR as well as WNT pathway proteins. The samples were further classified based on their proliferation status and the expression of these oncoproteins was also observed. In order to compare the cytological data with histological data, 30 OL patients undergoing biopsy were chosen and immunohistological analysis was performed for the same pathways. Results showed overexpressing EGFR and WNT pathway proteins in all OL samples. Structurally atypic cells had a tendency to overexpress these oncoproteins. However the immunocytochemistry data could not confirm any positive effect of chewing tobacco on the OL's proliferative state. Statistical data from the immunfluorescence finally revealed the overexpression of both EGFR and WNT pathway proteins on the proliferative population establishing chewing tobacco as a positive risk factor for the onset of OL. Data from biopsy samples followed the same trend of protein expression seen in the cytological samples. Dysplastic zones showed huge overexpression of EGFR and WNT pathway proteins among tobacco chewers. In conclusion, this is the first time report showing the effect of chewing tobacco on the EGFR and WNT pathway in OL and its possible role as a potential risk factor for its proliferative type.

Close to 12 million people in India are affected by more than the desirable level of fluoride in drinking water that could lead to dental, skeletal, and non-skeletal fluorosis. Dental fluorosis is a developmental defect that results in hypo-mineralization and pronounced porosity of enamel in the affected individuals. As estrogen receptor 1 (ESR1), collagen type 1 alpha 2 (COL1A2), bone γ-carboxyglutamic acid protein (BGLAP), and secreted protein acidic and cysteine rich (SPARC) genes are involved in bone development and mineralization, polymorphisms in these genes could be determining factors in influencing the risk to fluorosis among the exposed individuals in fluoride endemic areas. A case-control study was carried out among a total of 87 individuals (case = 36, control = 51) to examine the association between selected polymorphisms in the ESR1, COL1A2, BGLAP, and SPARC genes and risk of dental fluorosis from a fluoride endemic region of Eastern India. Altogether, 10 single nucleotide polymorphisms (SNPs) in ESR1 (rs2234693, rs2228480, rs3798577, rs2077647, and rs9340799), COL1A2 (rs42524, rs412777), BGLAP (rs1800247), and SPARC (rs6579885, rs4958278) genes were genotyped through PCR-RFLP in these subjects. The association of the SNPs for disease risk estimation was measured by odds ratio with 95% confidence interval. The risk genotypes of none of the 10 SNPs showed statistically significant association with risk of dental fluorosis. Frequencies of the haplotypes in the intragenic SNPs of the ESR1, COL1A2, and SPARC genes did not reveal any statistically significant difference between the case and control groups. The present study is the first of its kind from India that has attempted to investigate possible involvement of genetic factors in influencing the risk to fluorosis among the population from a fluoride endemic region.

Fluorosis, caused by ingestion of excess fluoride, is endemic in at least 25 countries across the globe, China and India being the worst affected among them. Dental, skeletal and non-skeletal are the major types of fluorosis affecting millions of people in these countries. A number of genetic epidemiological studies carried out by investigators have shown the evidence for association between genetic polymorphisms in candidate genes and differences in the susceptibility pattern of different types of fluorosis among individuals living in the same community and having the same environmental exposure. These studies have pointed out that genetic variants in some candidate genes like COL1A2 (Collagen type 1 alpha 2), CTR (Calcitonin receptor gene), ESR (Estrogen receptor), COMT (Catechol-o-methyltransferase), GSTP1 (Glutathione S-transferase pi 1), MMP-2 (Matrix metallopeptidase 2), PRL (Prolactin), VDR (Vitamin D receptor) and MPO (Myeloperoxidase) could increase or decrease the risk of fluorosis among the exposed individuals in endemic areas. So, it is increasingly becoming evident that an individual's genetic background could play a major role in influencing the risk to fluorosis when other factors like specific environmental exposures including dietary patterns of fluoride intake and other nutrients remain the same. The current manuscript presents an up-to-date critical review on fluorosis, focusing mainly on the genetic association studies that have looked at the possible involvement of genetic factors in fluorosis.